Oh the irony ....just as many (often in the UK) were clamouring for the DSM-5 to dispense with so-called Attenuated Psychosis Syndrome (which they did reject), the Brits sneaked it in through the back door as (Ultra) High Risk for Psychosis in the new NICE guidelines for Psychosis and Schizophrenia in Children and Young People. In their 485 page guide, NICE advise on 'treatment' for those aged between under 18 (estimates suggest a 0.4% prevalence of psychotic disorders in children aged between 5 and 18 years)

The cliche states that 'An ounce of prevention is worth a pound of cure' and a recent meta-analysis (Open Access in BMJ) examines whether various interventions might prevent or delay transition to psychotic disorders for people at 'High Risk'. The paper was written by some members of the NICE committee who prepared the guideline for children and young people; and underpins some of their decision making process...so, is worthy of closer inspection

I want to focus on their recommendation - CBT - as their conclusion implies CBT is the best course of 'action' for preventing transition to psychosis

Stafford et al declare that "Among people at “ultra high risk” of psychosis, about 22% to 40% transition within 12 months [and that]Interventions that delay or prevent transition to psychosis from this prodromal syndrome could be clinically and economically important." Unquestionably, if up to 40% of those who would go on to develop psychosis (schizophrenia) could receive an intervention to delay or even prevent such a transition, this might be viewed as a worthy ambition.

What is (Ultra) High Risk and what did Stafford et al do?

Stafford et al meta-analysed 5 studies examining people "judged to be at risk of developing psychosis on the basis on a clinical assessment identifying prodromal features."

and they conclude that Cognitive Behavioural Therapy has the effect of "reducing transition to psychosis at 12 months (risk ratio 0.54 (95% confidence interval 0.34 to 0.86); risk difference −0.07 (−0.14 to −0.01)."

1) The authors report that the Risk Difference is -0.07. This means that CBT produces a 7% reduced risk for transition to psychosis compared to control. To translate this into another common metric, the Number Needed to Treat (NNT), an average of 14 people need to be treated with CBT to prevent one person developing psychosis - this NNT is somewhat larger than typically claimed by individual studies!

Figure 1. Risk Ratios for Number of transitions to psychosis in CBT vs supportive counselling

2) As can be seen in Fig 1, the small significant effect reflects the pooling of 5 studies; however, none of the five studies were themselves significant! The wonderful world of meta analysis (I have referred to this phenomenon previously in my blogs on using LSD to treat alcholism and how to deal with negative findings

Figure 1 also shows that the transition rate is extremely small in these studies - nowhere near the heights of 40% but closer to 10% on average. In other words, 90% of the identified High Risk individuals do not develop psychosis at all! In this context, we need to seriously consider the risks of labelling 9/10 people as High Risk when they are not! The stigma of being labelled High Risk was one major complaint about adding Attenuated Psychosis Syndrome to the DSM-5. As McGorry et al (2003) rightly state "most cases of first episode psychosis still come from the low-risk and undetected groups" (p.784) - not from the ironically entitled 'Ultra High Risk'!

3) Although the NNT and Risk Difference figures are not overly impressive, they do appear to record a significant effect. Nonetheless, the difference between CBT and control in conversion rates disappears beyond 12 months i.e. the point at which this meta-analysis terminates. As the authors state:

"At 18 months, there was low quality evidence that CBT is associated with fewer transitions (0.63 (0.40 to 0.99)), and the effect did not remain significant in sensitivity analysis (0.55 (0.25 to 1.19))."

If a small effect of CBT disappears beyond 12 month comparisons - how useful is it? And why stop at 12 months?

4) Analysis of the effects of CBT on symptoms of psychosis is also worth considering in transition studies and the authors did examine this.

"Combined effects for positive symptoms of psychosis, depression, and quality of life were not significant at any time point."

To reiterate, CBT did not impact symptoms at all!

5) Finally, the authors claim that all of the 5 included studies were high quality (having excluded others for example, for lack of blinding for raters at outcome). Their Figure 2 (see below) indicates that the 5 CBT studies (Addington 2011; Morrison 2004; Morrison 2011; Phillips 2009 and van der Gaag 2011), were all blind at outcome assessment (see blinding of outcome assessment column)

However, the Morrison et al (2004) study was not blinded at outcome - as they say in that 2004 paper

"Assessors were intended to be masked to the condition to which the patient was allocated; however, this proved difficult in practice because the participants often divulged information about their therapist, or used language that suggested they were receiving cognitive therapy...It proved impossible fully to maintain masking to treatment allocation for assessment of the primary outcome" Morrison et al (2004)

It seems somewhat odd to make such a mistake- as Morrison one of the authors of this current meta-analysis! Removing Morrison et al (2004) from the analysis reduces the Risk Ratio (RR=.60 [.37 to 0.99) which now becomes marginally significant (p=.044) and suggests that the NNT with CBT would be 22 to stop one psychosis transition.
To conclude, it seems that Ultra High Risk for Psychosis, which has been sneaked into NICE guidelines for children and the young, has a limited application - probably less than 1 in 10 individuals actually convert. Moreover, the claim that CBT provides the best form of 'treatment' also seems unsubstantiated. As usual, I am sure we will hear claims for further, better, larger trials - to justify the conclusion already made!

8 comments:

cbt doesnt claim to reduce symptoms does it? just ameliorate the stress they cause and improve understanding of them. psychotic episode or "relapse" are crap surrogate markers for treatment failure. though i admit QOL is reported as not being improved.

a NNT of 7-14 isn't bad, the NTT for aspirin in heart attacks is about 20-50. i admit its hard to capture a specific group of "ultra high risk" people but we see this in many other conditions, some people just get lung cancer without smoking one cigarrete.

and psychotic episodes are traumatic and expensive++, may well be acceptable from a cost/benefit approach.

as for your comments re:many negative results making a positive being illogical? come on now, thats the whole point of a meta analysis, every study was pointing towards a positive effect but was underpowered. basics.

Thanks for your comments - I will take each in turn.The near 40 RCTs of CBT for psychosis over the past 20 years have *all* focussed on reducing symptoms - and this has been the big claim.

I know of no evidence that CBT reduces stress associated with psychosis - can you recommend studies or a relevant meta analysis?

The NNT is not 7-14, but more like 22 as I suggested above! And, one more conversion in the CBT group would make the effect totally nonsignificant at 12 months anyway!In any case, CBT has no impact at all on conversion beyond 12 months - so it is irrelevant because the NNT then becomes infinity

No evidence on the cost-benefit of CBT here - so we cant say - though it seems to have next to no benefit with some cost - plus we need to see studies on the adverse effects of CBT

Re meta analysis - its not the point to pool negative studies to make a positive overall effect - and indeed, where that has occured in medicine, large trials and subsequently typically shown effects to be nonsignificant. And what would be the adequate sample size anyway - Morrison et al have 288 participants, van der Gaag has 200+ - both are nonsignficant (as is the Morriosn et al follow not included here)- How many are needed?

Fantastic blogs,thank you. As a Mental Health Nursing student we are encouraged to take a progressive view. From post-psychiatry, auto-ethnography to psycho-dynamic approaches and talking therapies of which CBT seems to be favored on mass by those who have influence (politicians/academics) so it is good to see this slightly coercive view of CBT is being challenged.

The opportunity to have a talking therapy before CBT for Psychosis for people with psychosis did not exist. From the origins of psychotherapy people in distress with hallucinations, or voices, delusions or distressing beliefs they were left often distressed isolated and disenfranchised. The rhetoric of psychoanalysis (how many RCTs is that founded on?) labelling the psychotic as too ill. (with the exception of Wilfred Bion)

As someone sectioned with psychosis at 19, and with 3 complusory more admissions before having CBT for psychosis and one during it. I have been well for over ten years have a stable relationship have two children. As a mental health professional I am training as a CBT for Psychosis therapist.

It is not the Meta analysis that I would question about your article Professor Keith Laws, everyone would like better results, they are limited and but are showing a consistent limited effect. (If I had been part of a trial I would have been a readmission!)

It is to wonder why the vitriol in you dogged attacks on CBT for psychosis without offering any alternative.

The researchers loom like demons coercing people into CBT.

The therapy focusses on distress and allevating the distress of psychosis. It is affectionate, and like Jonathon Richmond and theodern lovers say " we must show some affection and to me this is real, to me this aint funny, so i thought I would tell everybody about how feel

http://www.youtube.com/watch?v=yb1Stzo6Riay

CBT for psychosis needs further development and is under going developments. People choose to come to sessions and it is centred on their goals.

Personally I am glad for the fact that politicians, economists and heath policy makers are now piloting IAPT SMI who else is supporting talking to people in distress to help them get on with their lives

Thanks Ben. I will address you comment about "why the vitriol in your dogged attacks on CBT for psychosis without offering any alternative"

Cant see why you think I am "vitriolic" but ....CBT for psychosis studies are frequently based on poor science and use spinning and clinicians show a poor understanding of the underlying science and evidence - these are my issues - I have shown plenty of examples where these factors are evident here and elsewhere on my blog.

Re not providing an alternative - I have been quite clear in stating that 'befriending' (or supportive counseling) is as minimally effective as CBT for psychosis - it is cheaper in every respect (from training through to cost of sessions), its simpler, and less theoretically laden

The various meta-analyses show that there is a small effect size for CBTp especially on distress. There are new things being researched, Low intensity CBTp, sleep, worry, reasoning biases, command trial for command hallucinations.

I dont reaally see it as a demon, or coercive, it is like physio you go along you have some personal goals you work towards them.